Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis

• Published in: Journal of medicinal chemistry 2022-01, Vol.65 (2), p.1047-1131
• Main Authors: Ayala-Aguilera, Cecilia C, Valero, Teresa, Lorente-Macías, Álvaro, Baillache, Daniel J, Croke, Stephen, Unciti-Broceta, Asier
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - therapeutic use; Drug Approval; Humans; Neoplasms - drug therapy; Neoplasms - enzymology; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - therapeutic use; Small Molecule Libraries - chemical synthesis; Small Molecule Libraries - therapeutic use; United States; United States Food and Drug Administration
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.1c00963

The central role of dysregulated kinase activity in the etiology of progressive disorders, including cancer, has fostered incremental efforts on drug discovery programs over the past 40 years. As a result, kinase inhibitors are today one of the most important classes of drugs. The FDA approved 73 small molecule kinase inhibitor drugs until September 2021, and additional inhibitors were approved by other regulatory agencies during that time. To complement the published literature on clinical kinase inhibitors, we have prepared a review that recaps this large data set into an accessible format for the medicinal chemistry community. Along with the therapeutic and pharmacological properties of each kinase inhibitor approved across the world until 2020, we provide the synthesis routes originally used during the discovery phase, many of which were only available in patent applications. In the last section, we also provide an update on kinase inhibitor drugs approved in 2021.